Cancer Genes: Volume 2

By Satish Ramalingam

Cancer Genes is a comprehensive list of the most critical genes known to contribute to cancer imitation and progression. The book delves into their location on each chromosome, providing valuable insights into the mechanisms of cancer gene dysregulation and genetic mutations which provide cancer cells with an advantage during each stage of tumorigenesis. The reference will familiarize readers with the location of cancer genes and equip them with the necessary information to identify relevant gene expression targets for research aimed at preventing the disease. The book is divided into two volumes focusing on cancer-causing genes found in chromosome pairs 1-12 (volume 1), and chromosomes13-23 (volume 2). A key feature of the book is a detailed reference list for advanced readers. The compilation is therefore a quick and handy reference on cancer-causing genes for researchers, medical professionals, and anyone interested in understanding the genetic basis of cancer.

• Language: English
• Publisher: Bentham Science Publishers
• Release date: Feb 2, 2000
• ISBN: 9789815136500

Book preview

Chromosome 13

Aishwarya Raja¹, Ravi Gor¹, Saurav Panicker¹, Satish Ramalingam¹, *

¹ Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, India

Abstract

Chromosome 13 represents around 4 percent of the total cellular DNA with 115 million base pairs. It is home to various tumor suppressors and oncogenes, such as ADP ribosylation factors like GTPase-11 (ARL11), Retinoblastoma-1 (RB1), Ras-related protein Rap-2a (RAP2A), etc. Most of the somatic mutations in this chromo-some lead to cancer development. Further, deletion in this chromosome has been reported to support the cancer of leukemias, lymphomas, etc. In this chapter, we have tried to list cancer-causing genes and their possible oncogenesis in cancer development.

Keywords: ADP Ribosylation Factors Like GTPase-11, Cancer, Gene Deletion, Leukemia, Lymphomas, Oncogene, Ras-Related Protein Rap-2a, Retinoblastoma-1, Tumor Suppressor, Tumor Suppressor.

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* Corresponding author Satish Ramalingam: Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, India; E-mail: [e-mail]

1. ABCC4- ATP Binding Cassette Subfamily C Member 4 Chromosome 13; 13q32.1

ATP-binding cassette sub-family C member 4 [ABCC4], also known as the multidrug resistance-associated protein 4 [MRP4] or multi-specific organic anion transporter B [MOAT-B], is a protein that in humans is encoded by the ABCC4 gene [1]. MRP4 confers resistance to acyclic nucleoside monophosphates, such as 9-[2-phosphonylmethoxyethyl] guanine [PMEG], and to the anti-HIV drug, 9-[2- phosphonylmethoxyethyl] adenine [PMEA] [2]. ABCC4 protein is present in humans' kidneys, liver, erythrocytes, adrenal glands, platelets, brain, and pancreas [3].

2. ARL11- ADP Ribosylation Factor like GTPase 11 Chromo-some: 13; 13q14.2

ARL11, also known as ADP-ribosylation factor-like tumor suppressor gene 1 [ARLTS1], is a member of the Arf-like [ARL] family of small GTP-binding prot-

eins that regulate diverse cellular processes, including vesicular trafficking, cytoskeletal organization, signaling, and ciliogenesis [4]. Further support for its tumor suppressor function has come from the finding that SNPs G446A [W149X] and T442C [C148R] in the ARL11 gene are associated with familial risk for chronic lymphocytic leukemia [CLL] and breast, prostate, and colorectal cancers [5].

Fig. (1))

This figure displays the loci of the genes from Chromosome 13 whose roles in cancer have been explained in this chapter. Sayooj Madhusoodanan designed this diagram.

3. AT7B - ATPase Copper Transporting Beta Chromosome: 13; 13q14.3

This gene (Fig. 1) is a P-type cation transport ATPase family member and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least 2 puta-tive copper-binding sites. This protein functions as a monomer, exporting copper out of the cells, such as the efflux of hepatic copper into the bile. The ATP7B product, a protein of 1465 amino acids [ATP7B], is expressed predominantly in humans’ liver, kidney, and placenta [6]. ATP7B was overexpressed in cisplatin-resistant prostate carcinoma PC-5 cells but not in the parental PC-3 cells and the revertant PC-5R cells. ATP7B may be involved in cisplatin resistance in some tumors [7].

4. BRCA2- Breast Cancer Gene 2 Chromosome 13; 13q13.1

This gene (Fig. 1) helps make a breast tumor suppressor protein. BRCA2 is involved in repairing damaged DNA by interacting with several other proteins in the nucleus to mend the damaged DNA. Mutations in this gene cause breast cancer [8]. The BRCA2 gene interacts with the recombinase enzyme and stimulates and maintains strand invasion [9]. It is expressed in breast tissues and other cells and destroys cells if the DNA is not repaired [10].

5. CCNA1- Cycline A1 Chromosome 13; 13q13.3

The Cycline A1 protein encoded by this gene (Fig. 1) is expressed in the testis, brain, and several leukemic cell lines and controls meiosis. This protein binds to Rb family proteins, the E2F1 transcription factor and the Kip/Cip family of CDK- inhibitor proteins [11]. They activate the subunits of enzymatic complexes with CDKs [12]. CCNA1 gene-associated diseases include myeloid leukemia and testicular cancer [13].

6. CDX2- Caudal Type Homeobox 2 Chromosome 13;13q12.2

This gene (Fig. 1) produces homeobox caudal transcriptional factor protein expre-ssed in the intestinal epithelial cells [14]. It helps in embryonic development, regulation, proliferation and differentiation of intestinal epithelial cells in the adult. CDX2 ectopic expression was found in acute myeloid leukemia [15]. CDX2 is used as a biological marker for detecting intestinal cancer [16]. It is found to be expressed only in intestinal cells.

7. COL4A2- Collagen, Type IV, Alpha 2 Chromosome 13; 13q34

This gene (Fig. 1) encodes for Collagen alpha-2[IV] chain protein which forms the glomerular basement membrane with COL4A1 and is present in all organs. It is also a biomarker for gastric cancer [17] and esophagus [18]. The C-terminal of the protein is an inhibitor of angiogenesis and tumor growth [19]. Mutations cause intracerebral hemorrhage [ICH] [20].

8. CUL4A- Cullin 4 Alpha Chromosome 13; 13q34

Cul 4a is a ubiquitin ligase component involved in DNA damage-response protein degradation [21]. Cullin 4A helps in cell growth, and development and is essential in chaperone-mediated ubiquitination, and it interacts with TP53 in carcinogenesis [22]. CUL4A inhibition was done in primary breast cancer cells by thalidomide which suppressed the EMT process that is induced by TGF-β1 [23].

9. DACH1- Dachshund Family Transcription Factor 1 Chromosome 13; 13q21

Reduced expression of the DACH1 gene was found in breast, prostate, lung, and brain tumors. Expression of cyclin D1 inhibited by the DACH1 gene reduces breast cancer cell growth [24]. The DACH1 gene has 12 exons and spans 400 kb [25]. DACH1 was highly expressed in adult and embryonic kidney tissues [26].

10. DLEU2- Deleted in Lymphocytic Leukemia 1 Chromo-some 13; 13q14

DLEU2 is a tumor suppressor gene found suppressed in leukemia and a negative regulator of cell proliferation [27]. Overexpression-induced pancreatic cancer cell proliferation and invasion and knockdown of DLEU2 impaired cell proliferation and invasion in vitro [28].

11. EDNRB- Endothelin Receptor Type B Chromosome 13; 13q22.3

This gene produces a protein called endothelin receptor type B, which helps in the signaling mechanism in cells [29]. EDNRB is a tumor suppressor gene down-regulated by promoter hypermethylation [30]. EDNRB gene transcription is down-regulated during tumor development, altering the ET1 signaling pathway [31].

12. EFNB2- Ephrin B2 Chromosome 13; 13q33.3

EFNB2 gene encodes for ephrin B2 protein [32]. It is also a receptor for Nipah and Hendra virus studies [33]. In uterine cervical cancer, this gene is used as a prognostic marker [34].

13. ERCC5 - Excision repair Cross-Complementing Repair 5 Chromosome 13; 13q33.1

This gene encodes DNA repair complementing XP-G cells [35]. This gene is involved in the repair of interstrand crosslinks and DNA repairs of UV-induced damage in cells [36]. Arthrogryposis multiplex congenital [AMC] is caused due to mutations in the ERCC5 gene [37]. Mutations in this gene also cause Xeroderma pigmentosum and Cockayne syndrome [38].

14. FGF9- Fibroblast Growth Factor 9 Chromo-some 13; 13q12.11

This gene produces a fibroblast growth factor family protein which helps in glial cell development [39]. FGF9 gene mutations cause diminished lung epithelial branching [40] and stimulate chondrocyte proliferation [41]. FGF9 gene mutati-ons also cause abnormal sex determinations [42].

15. FLT1- Fms Related Receptor Tyrosine Kinase 1 Chromo-some 13; 13q12.3

FLT1 gene encodes the vascular endothelial growth factor receptor 1 protein [43]. VEGF plays a vital role in the pathogenesis of hepatocellular carcinoma [HCC] [44]. VEGF-receptor genes were upregulated in canine tumor tissues but not normal tissues [45].

16. FLT3- Fms-Related Tyrosine Kinase 3 Chromosome 13; 13q12.2

Fms-like tyrosine kinase 3, called cluster of differentiation antigen 135 [CD135] protein, is produced by the FLT3 gene. This protein is a receptor for the cytokine Flt3 ligand. Mutations in this gene usually cause acute myeloid leukemia [AML] [46]. It consists of 5 immunoglobulin domains and is used as cell surface markers for hematopoietic progenitors in the bone marrow. FLT3 is a ligand-activated receptor tyrosine kinase expressed by hematopoietic stem and helps in the early development of myeloid and lymphoid lineage [47].

17. FOXO1- Forkhead Box O1 Chromosome 13; 13q14.11

Forkhead box protein O1 was produced by the FOXO1 gene [48]. Gluconeog-enesis and glycogenolysis regulation in adipogenesis was carried out by the FOXO1 gene [49]. This gene on high expression in human LNCaP prostate cancer cells leads to apoptosis [50]. The inactivation of the FOXO1 gene causes many types of human cancer [51].

18. GAS6 - Growth Arrest-Specific 6 Chromosome 13; 13q34

The Gas6 gene belongs to the vitamin K-dependent family of proteins that regul-ate cell proliferation, migration, and survival by Tyro3, Axl, and Mer rece-ptor binding [52]. It is a 678-amino acid protein with a high affinity to the Axl receptor [53]. Cell proliferation and differentiation, migration, and cellular signaling are regulated by Gas6 interaction with Tyro3, Axl, and Mer [TAM] receptors through its sex hormone-binding globulin [SHBG] [54].

19. GJB2- Gap Junction Protein Beta 2 Chromosome 13; 13q12.11

GJB2 gene encodes for connexin protein in humans. Connexin acts as a Tumor suppressor, and mutations in this gene result in different cancers, such as colorectal cancer, breast cancer, and bladder cancer [55]. Overexpression of this gene helps in cancer cell migration and invasion [56]. HMGB1- High Mobility Group Box 1 Chromosome 13; Location: 13q12.3. This gene encodes high-mobility group protein 1 [HMG-1] and amphoterin [57]. HMGB1 gene is used as a cancer target gene as it interacts with P53 [58]. Receptors such as TLR2, TLR4, and RAGE interacts with HMGB1 and helps in cell activation [59].

20. IFT88 – Intra Flagellar Transport Protein 88 Chromo-some 13; 13q12.11

Intraflagellar transport protein is encoded by the IFT88 gene [60]. This gene interacts with BAT2 and WDR62 genes, which are used in the localization of the IFT88 gene [61]. IFT88 protein is involved in the metabolic remodeling of cancer cells [62].

21. ING1- Inhibitor of Growth Protein1 Chromosome 13; 13q34

This gene can act as a tumor suppressor gene that induces cell growth arrest and apoptosis. This protein interacts with TP53 and helps in the p53 signaling pathway. Reduced expression of this gene is found in many cancers [63]. Interacts with p53/TP53 to negatively regulate the cell growth pathway by modulating p53- dependent transcriptional activation [64].

22. IRS2- Insulin Receptor Substrate 2 Chromosome 13; 13q34

IRS2 gene encodes insulin receptor substrate 2 for mediating insulin-like growth factors by acting as a receptor for tyrosine kinases and other effectors. The end product is phosphorylated by insulin receptor tyrosine kinase and interleukin 4 receptor-associated kinases during IL4 treatment [65]. Overexpression of IRS2 was found to promote tumor metastasis [66]. IRS1 has high expressivity in ductal carcinoma in situ [DCIS] and breast cancer cells with high invasiveness [67].

23. KL- Klotho Chromosome 13; 13q13.1

Klotho enzyme was encoded by KL gene1 and consisted of three divisions: α- klotho, β-klotho and γ-klotho [68]. The FGF23 gene was activated by α-klotho, and β-klotho activates the FGF19 and FGF21 genes [69]. Klotho is a β-glucu-ronidase that helps in aging and controlling insulin secretion [70].

24. KLF5- Krueppel- like Factor 5 Chromosome 13; Loca-tion: 13q22.1

KLF5 gene with RP1 enhances growth in breast cancer by suppressing p27kip [71]. Klf4 is a Yamanaka factor used to reprogram somatic cells to a pluripotent state [72]. KLF5 interacting with SET protein leads to negative regulation of KLF5 DNA binding, transactivation, and cell proliferation [73].

25. LAMP1- Lysosomal Associated Membrane Protein 1 Chromosome 13; Location: 13q34

LAMP1 is a transmembrane protein expressed at high levels in different tissue cell types and mainly in lysosomal membranes [74]. It is a 40kDa polypeptide with Polylactosamine to protect from lysosomal proteases [75]. It is found predominantly in pancreatic cancer, colon cancer, and melanoma and helps in cell adhesion and migration [76].

26. LATS2- Large Tumor Suppressor Kinase 2 Chromosome 13; Location: 13q12.11

It acts as a negative regulator of YAP1 in the Hippo signaling pathway that helps control growth and tumor suppression [77]. It is a 120kDa protein that localizes to centrosomes during interphase and early and late metaphase [78].

27. LCP1- Lymphocyte Cytosolic Protein 1 Chromosome 13; Location: 13q12.11

This gene encodes plastin 2 protein in humans [79]. These are actin-binding proteins upregulated in metastatic colon cancer cell line SW620 than SW480 cell lines [80]. This gene has been identified in various tumors such as prostate, colon, breast cancer, and oral squamous cell carcinomas [81].

28. LHFP- Lipoma HMGIC Fusion Partner Chromosome 13; Location: 13q13.3-q14.11

It is a part of the tetraspan transmembrane protein encoding genes such as LHFPL6 [LHFPL Tetraspan Subfamily Member 6] [82]. Mutations in this gene cause deafness in humans. Diseases caused by LHFPL6 include Gliosarcoma and Infiltrating Lipoma. LFHPL1 is a paralog of LHFPL6 gene [83].

29. LIG4- DNA Ligase 4 Chromosome 13; Location: 13q33.3

LIG4 gene in humans encodes for the DNA ligase 4 enzyme [84]. Lig4 interacts with XRCC4 and DNA-dependent protein kinase [DNA-PK] for the NHEJ pathway. Defects in this gene cause LIG4 syndrome. LIF4 stimulates the adenyl-ation of XRCC4 and XLF [85].

30. MIR1297 - microRNA 1297 Chromosome 13; Location: 13q-14.3

The MIR1297 gene acts as a tumor suppressor and is oncogenic in different conditions. For example, in lung cancer, it inhibits cell proliferation, whereas, in head and neck cancer, it promotes cell proliferation, cell migration, and tumor genesis [86]. MIR1297 also acts as a tumor suppressor in hepatocellular carcin-oma by apoptosis and targeting the HMGA2 gene. In breast cancer, MIR1297 acts as a prognostic cell marker [87].

31. OLFM4- Olfactomedin 4 Chromosome 13; Location: 13q-14.3

The protein encoded by this gene is oncogenic by promoting cell adhesion. It also acts as a marker for metastatic breast cancers [88]. This gene is highly expressed in colon cells and is cloned from myeloblasts. In hepatocellular carcinoma, this gene promotes tumor growth by GRIM19 expression [89].

32. PDX1- Pancreatic and Duodenal Homeobox 1 Chromo-some 13; Location: 13q12.1

This gene plays a vital role in pancreatic development and duodenal cell differe-ntiation. In gastric cells, the absence of PDX1-encoded protein leads to tumor growth. Expression of PDX1 is found to inhibit tumor cell proliferation [90]. This gene acts as a regulator for β cell maturation and function. In Pancreatic ductal adenocarcinoma [PDAC], PDX1 acts as a cancer cell marker, and it is also found to promote insulinoma in human insulinoma cell lines [91].

33. POSTN- Periostin Chromosome 13; Location: 13q13.3

Periostin is the protein encoded by the POSTN gene. In cancer cells, periostin acts as a ligand activating FAK-mediated pathways leading to increased cancer cell proliferation [92]. Periostin forms various isomers that are specific to colon, breast, and pancreatic cancers [93]. Periostin enhances tumor growth by suppo-rting M2 tumor-associated macrophages in signaling [94].

34. RAP2A- Ras-Related Protein Rap-2a Chromosome 13; Location: 13q32.1

RAP2A is an isoform or RAP2 which belongs to the GTPase family. Rap 2a is a RAS oncogenic family protein encoded by the RAP2A gene [95]. This gene helps in cell proliferation, migration, and other cellular activities. Rap 2 protein on activated by DNA damage and gets transcribed by p53. It also acts as a target for the p53 transcription factor [96].

35. RB1- Retinoblastoma Transcriptional Corepressor 1 Chromosome 13; Location: 13q14.2

RB1 encodes retinoblastoma protein [RB] and acts as a tumor suppressor in many cancers. In cancer treatment, retinoblastoma protein enhances the effects of CDK4 & CDK6 inhibitors [97]. RB1 tumor suppressor activity was studied in mice by Rb-knockdown in hair cells [98].

36. SACS- Sacsin Molecular Chaperone Chromosome 13; Location: 13q12.12

The SACS gene encodes Sacsin protein, consisting of HEPN and DnaJ domains. This gene is found in the skin, pancreas, and nerves. This gene interferes with Hsp and the ubiquitin-proteasome system [99]. Mutations in the SAC gene are rare and cause different cancer types. Mitotic delay causes tumor genesis [100].

37. SOX1- SRY-Box Transcription Factor 1 Chromosome 13; Location: 13q34

The protein encoded by the SOX1 gene is a transcriptional activator. The methyl-ated form of this gene promoter is used as a biomarker in studying hepatocellular carcinoma [101] and also acts as a tumor suppressor by inhibiting the WNT/β-catenin pathway in hepatocellular carcinoma [102].

38. SPRY2- Sprouty 2 Chromosome 13; Location: 13q31.1

SPRY2 gene encodes the sprouty 2 protein that interacts with Cas-Br-M in murine cells. This gene helps in K-rasG12D-mediated regulation in murine cells [103]. High gene expression in mice leads to inhibition of lung epithelium tumor genesis [104].

39. STARD13- StAR-Related Lipid Transfer Domain Protein 13 Chromosome 13; Location: 13q13.1-q13.2

The protein encoded by this gene activates GTPases, mostly Rho A and CDC42 [105]. It acts as a tumor suppressor gene in breast cancers by reacting with ceRNA networks [106].

CONCLUSION

We have listed cancer-causing genes from chromosome 13, and we found a combination of genes. The tumor suppressor, oncogene, chemo-resistant gene, etc., are present in chromosome 13. For example, the ARL11, a tumor suppressor gene, SNP mutation in this gene will lead to the development of breast cancer, prostate cancer, colorectal cancer, etc. A chemo-resistance gene is also present in this chromosome called ATP7B. Overexpression of the ATP7B gene promotes resistance against cisplatin treatment in prostate cancer patients. Several prognostic markers are also present in this chromosome, including the BRCA2, RB1, EFNB2, etc. It shows that this chromosome is responsible for and plays a role in a variety of cancer. Further, any abnormality in it may cause the development and progression of cancer.

REFERENCES

Chromosome 14

Harini Hariharan¹, Saurav Panicker¹, Satish Ramalingam¹, *

¹ Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, India

Abstract

Cancer genetics has focused on several mutational events within a tumor cell for many years. Recently, the study on cancer genetics has been widened by concentrating on the importance of intercellular communication and epigenetic events causing tumor progression and development. The translocation of genetic material betwixt chromosome 14 and other chromosomes may engender the formation of various types of tumors. Recent studies emphasize that these chief translocations between two chromosomes may disrupt the genes crucial for controlling cell growth and cell division. The translocations involving chromosome-14 and other chromosomes have been found in tumors including acute myeloid Leukemia, acute lymphoblastic leukemia, acute bilineal leukemia, follicular lymphoma, small cell lung cancer, non-Hodgkin’s lymphoma, Burkitt lymphoma and multiple myeloma. The tumor suppressor genes, such as ARID4A, ARID4B, BCL11B, BMP4, CCNB1IP1, CEBPE, DICER1, DLK1, ESR2, FOXN3, HIF1A, MAX, MEG3, NDRG2 and TTF-1/NKX2-1 under chromosome 14, play a hypercritical role by enhancing cellular differentiation, migration, proliferation, metastasis, invasion, cellular growth, and development in several tumors, including breast cancer, pancreatic tumor, osteosarcoma, lung cancer, endocrine tumor, T-ALL, cystic nephroma, Hodgkin lymphoma, pleuropulmonary blastomas, Sertoli Leydig ovarian tumors and rhabdomyosarcoma. Chapter 14 meticulously discusses the importance of each predominant gene under chromosome 14 in mediating tumorigenesis. In cancer genetics, these cardinal genes play a crucial role by acting as an oncogene or a tumor suppressor in several cancers. Thus, targeting these tumor-causing genes would provide a breakthrough in cancer biology and oncology when concerned with future perspectives.

Keywords: Burkitt lymphoma, Cellular differentiation, Cystic nephroma, Epigenetic events, Follicular lymphoma, Hodgkin’s lymphoma, Intercellular communication, Oncogene, Rhabdomyosarcoma, Translocations, Tumor supp-ressor.

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* Corresponding author Satish Ramalingam: Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, India; E-mail: [e-mail]

1. AKT1: AKT Serine/Threonine Kinase 1. Chromosome 14; 14q32.33

The three major isoforms of the serine-threonine kinase superfamily include AKT1, AKT2, and AKT3 [1]. AKT1 encodes a protein called PKBα [kinase B alpha protein] [1]. Recent studies emphasize that overexpression of the AKT signaling pathway is observed in almost 50% of human cancers [1].

Abnormal or altered gene expression levels of AKT signaling are predominantly found in tumors such as breast, non-small cell lung cancer, esophageal cancer, leukemic cancer, ovarian, colorectal cancer, and head and neck cancer [1, 2]. The SNPs identified in the AKT1 gene, including E319G rs12881616, P388T rs11555431, L357P rs11555432, E17K rs121434592, rs3803304 and rs2494732, are widely associated with tumor formation and migration [1]. On considering the enginery, the role of the AKT1 gene and its activation in tumor metabolism, recent studies hypothesize that the mTORC2 signaling pathway plays a pivotal role in phosphorylating and activating AKT1 gene at S473 in its carboxy terminus, wherein PDK1 phosphorylates AKT1 gene at T308 in its activation loop [1]. The activated AKT1 gene further phosphorylates certain downstream elements, which regulate tumor metabolism, apoptosis, cell growth, proliferation, and angiogenesis [1, 2]. Among the AKT1-associated SNPs, the rs3803304, an intronic noncoding variant, is superlatively correlated with breast tumor formation and development, suggesting that rs3803304 could be a prognostic biomarker in breast cancer formation [1]. Moreover, the mutation of AKT1E17K is found to be associated with HR-negative cancer cells with the relapsed condition [2]. Interestingly, the mutation of AKT1 E17K is not interrelated with lobular, medull-ary, ductal and mucinous histotypes [2]. The activation of the AKT gene in breast tumor cells showed elevated resistance to tamoxifen and trastuzumab treatment [3]. Higher expression of AKT is associated with early stages of sporadic colorectal carcinogenesis [4]. AKT1 gene expression is also mediated by Wnt/β-catenin signaling pathways [4]. The AKT1 transcription is mainly mediated by Tcf-Lef/ β-catenin in colorectal cancer [4]. Thus, the elevated expression of the AKT1 gene is associated with increased levels of nuclear β-catenin in sporadic colorectal cancer [4]. The amplification of AKT1 was first found in gastric cells, wherein in lung tumor cells, the AKT1 amplification leads to cisplatin resistance via the activation of the mTOR signaling pathway [3]. Though the regulation and activation of the AKT gene are almost found in 90% of non-small cell lung carcinoma, the AKT1E17K mutation transformation happens at a very low level in NSCLC [3].

2. APEX1: Apurinic/Apyrimidinic Endodeoxyribonuclease 1 Chromosome 14; 14q11.2

Redox factor 1, or APEX1, is a protein that possesses multifunctional charact-eristics and is involved in repairing apyrimidinic sites and ssDNA breaks [5]. APEX1 gene enhances the activation of the DNA-binding machinery of certain transcriptional factors involved in tumor progression and promotion, such as NF-kB, EGR1, PAX8, AP1, HLF, P53, and MYB [5]. Abnormal expression levels of APEX1 are usually associated with various solid tumors and their progression [5]. However, the actuation of the APEX1 gene in cancer progression is a hitherto [5]. Studies postulate that the expression levels of APEX1 are highly correlated with poor prognosis of cervical cancer, prostate cancer, colorectal cancer, osteosarcoma, hepatic cancer, and breast cancer [5]. APEX1 sustains tumor proliferation and cell viability in breast and colon tumor cells [5]. In an ovarian tumor, the depletion of the APEX1 gene attenuates the proliferation activity of the cells [5]. Interestingly, APEX1 implicates an antitumor activity in pancreatic tumor cells, like quelling tumor invasion, migration, and tumor growth [5]. As an upstream regulator and activator of the notch/ jagged1 signaling pathway, the APEX1 gene enhances the behavior of the colon tumor [5]. Meanwhile, elevated levels or knockout of APEX1 expression in colon tumors result in intense alter-ation of malignant characteristics in tumor cells, such as migration, metastasis, angiogenesis, proliferation, invasion, anchorage-independent growth, and tumor formation [5]. The carcinogenic activity of APEX1 is unraveled by its mode of enginery in up-regulating the jadded1 ligand in the notch signaling pathway [5]. Hence, APEX1 is a potential regulator of the jagged1 ligand and a curative target to treat colon tumors [5]. The mRNA expression levels of the APEX1 gene were notably higher in head and neck cancer cells in juxtaposed with control cells [6]. Surprisingly, the mutation and down-regulation of APEX1 caused a tremendous risk of head and neck cancer [6]. Widely known for its enhancement of DNA-binding machinery, APEX1 triggers the DNA-binding mechanism of NF-kB both in vitro and in vivo [6]. Depriving the APEX1 redox domain directly quells the TNF- mediated NF-kB regulation, which triggers TNF-mediated apoptosis of cells [6]. Recent studies emphasize that APEX1 expression in tumor cells may begin a perineural invasion and that APEX1 expression is relatively associated with gallbladder carcinoma [CaGB] formation [7].

3. ARID4A: AT-Rich Interaction Domain 4A Chromosome 14; 14q23.1

The natural phenomena of the ARID group are to activate transcription and are majorly indulged in cell proliferation and differentiation [8]. Hence, being an essential transcriptional regulator, ARID plays a crucial role in cellular differentiation, growth, and development [8]. ARID is considered a double-edged sword as it can either be a tumor suppressor or an oncogene in several mammalian malignancies [9]. ARID4 is subcategorized into two groups, namely ARID4A and ARID4B, respectively [8]. ARID4A is widely known as RBP1 or RBBP1 [retinoblastoma-binding protein 1] [9]. ARID4A is best known for its actuation in regulating cell growth [9]. The association of ARID4A with mSIN3-HDAC [mSIN3-histone deacetylase] and pRB [retinoblastoma protein] complex mediates migration and cell growth in several tumors [8]. ARID4A attaches the complex mSIN3-HDAC to the pRB group to suppress E2F-associated transcription and thereby plays an important role in ceasing cell growth [8]. The combined activity of mSIN3-HDAC and ARID4A with the metastasis suppressor-1 gene of breast tumor cells tends to suppress the transcriptional activity and several metastatic behaviors of certain tumors, respectively [8]. However, on a comprehensive view, the role and tendency of the ARID4A gene in tumor cells remain hitherto [8]. An epitope similar to ARID4A, named KASIFLK, is highly expressed in breast tumor tissues and cells, suggesting the importance of ARID4A as an oncogene [8]. Recent studies showed that the knockout of the ARID4A gene in the murine model resulted in leukemia formation, thus indicating the potential of the ARID4A gene as a leukemia tumor suppressor [8]. In gastric tumor cells, ARID4A predominantly targets miR-376c, inhibiting cell migration and proliferation [9]. In particular, the downregulation of ARID4A and ARID4B is widely associated with pancreatic tumors, thereby inducing cell migration and proliferation in pancreatic tumors [9]. Hence ARID4A and ARID4B acts as a tumor suppressor in pancreatic tumor [9]. Hurst at el. studied that the knockdown of ARID4A is directly involved in the repression of metastatic behavior of breast tumor cells [9]. It is estimated that ARID4A is associated with 4-52% of mutations and is considered the second most mutated gene-causing tumor [10]. ARID4A is found to be correlated with BRMS1 in breast tumor cells [9]. The expression levels of ARID4A are notably reduced in oral and laryngeal tumors compared with other cancers [10].

4. BCL11B: BAF Chromatin Remodeling Complex Subunit BCL11B Chromosome 14; 14q32.2

BCL11B, also known as B cell lymphoma or leukemia 11B, has a predominant role in T cell differentiation, development, survival, and proliferation [11]. The abnormal variations of BCL11B genes are widely interrelated with transforming T cells in bloodstream malignancies [11]. The top-notch activity of the BCL11B gene is to induce apoptotic behavior and trigger the proliferation of tumor cells [11]. The knockout of BCL11B causes T-ALL in humans and thymic lymphoma in murine models [11]. The BCL11B gene is considered to be a cancer suppressor, a haploinsufficient cancer repressor that tends to associate with T-ALL at the thymocyte transformation [11, 12]. In T-ALL cells, the siRNA-mediated BCL11B knockout results in the quelling of growth and apoptosis [11]. In a murine model, the knockout of BCL11B leads to lymphomagenesis, suggesting the role and ability of BCL11B knockout in developing human tumors [11]. The BCL11B gene is involved in the translocation between chromosome 6 and chromosome 14 at the locations q25-q26 and q32, which causes definite AML in humans [11]. Likewise, the translocation between chromosomes 5 and 14 at q35.1 and q32.2 is observed to cause ALL, T-ALL, and myeloid ABL [acute bilineal leukemia] in infant patients [11]. Heightened expression levels of BCL11B trigger a substantial opposition to apoptosis and induce resistance to chemotherapy via the accretion of T-ALL in the first phase of the cell cycle [Gap 1] [11]. Studies postulate that the superlative expression of BCL11B is known to be widely associated with Ewing sarcoma [12]. The knockout or reduced expression levels of BCL11B tends to trigger intestinal cancer and wherein, and the aberrant levels and mutation of BCL11B hypothesize the cause of colon tumors in humans [13]. Recent phenomenon proved that devitalizing the activity of the BCL11B gene tends to enhance the transcription via the wnt signaling pathway and triggers tumor formation in mice [13]. Hence, on the whole, BCL11B plays a vital role as a tumor suppressor in several cancers, and targeting the BCL11B gene would provide a breakthrough in tumor sciences concerning future aspects [13].

5. BCL2L2: BCL2 like 2 Chromosome 14; 14q11.2

BCL2L2 or BCL-W is a vital gene known for its pro-survival ability, which in turn causes several tumors [14]. Via its tremendous opposition to cell death, BCL-2 triggers tumorigenesis in many cells [15]. The increased expression of BCL2L2 is associated with many colon, gastric and cervical tumors [14]. In several cases,